Sagheer Usman, Shu Jian, Yu Hanjie, Ren Xiameng, Haroon Kashmala, Majeed Usman, Xu Chen, Zhang Fan, Xie Hailong, Li Zheng
Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, China.
School of Food and Biological Engineering, Jiangsu University, Zhenjiang 212013, China.
Int J Biol Macromol. 2025 May;306(Pt 3):141542. doi: 10.1016/j.ijbiomac.2025.141542. Epub 2025 Feb 27.
Despite medical advancements, lung cancer remains a leading cause of mortality, necessitating a deeper understanding. Recent studies show that protein glycopatterns and lung microbiome are crucial in lung cancer development, but their relationship in adenocarcinoma remains unexplored. Therefore, this study evaluated protein glycopatterns and microbial changes between lung adenocarcinoma (n = 70) and paracancerous tissues (n = 70) through lectin microarrays and 16S rDNA sequencing. Further, we explored the impact of protein glycopatterns against a decreased abundant microbiota using extracted glycoproteins reflecting high expression protein glycopatterns observed in lung adenocarcinoma tissues. The results demonstrated a significant up-regulation of protein glycopatterns in tumor tissues, including WGA binding to multivalent Sia/(GlcNAc)n (P = 0.0078) and Jacalin binding to T/Tn antigens (P = 0.0313). Meanwhile, two bacterial species of the genus Sphingomonas showed a significant decrease (P < 0.01) in adenocarcinoma as compared to paracancerous tissue. Interestingly, adhesion assay results showed glycoproteins (25-100 μg/ml) with multivalent Sia and (GlcNAc)n structures extracted by WGA-magnetic particle conjugates significantly reduce (P < 0.0001) Sphingomonas mucosissima adhesion and toxicity to lung cancer cells (A-549). The findings indicated that protein glycopatterns could inhibit cancer-instigating oncomicrobes to intercept cancer progression, offering insights into molecular mechanisms driving disease progression and aiding to develop new treatment strategies.
尽管医学取得了进步，但肺癌仍然是主要的死亡原因，这需要更深入的了解。最近的研究表明，蛋白质糖基模式和肺部微生物群在肺癌发展中至关重要，但它们在腺癌中的关系仍未得到探索。因此，本研究通过凝集素微阵列和16S rDNA测序评估了肺腺癌（n = 70）和癌旁组织（n = 70）之间的蛋白质糖基模式和微生物变化。此外，我们使用反映肺腺癌组织中观察到的高表达蛋白质糖基模式的提取糖蛋白，探讨了蛋白质糖基模式对丰度降低的微生物群的影响。结果表明，肿瘤组织中蛋白质糖基模式显著上调，包括麦胚凝集素（WGA）与多价唾液酸/（N-乙酰葡糖胺）n结合（P = 0.0078）以及红豆蔻凝集素与T/Tn抗原结合（P = 0.0313）。同时，与癌旁组织相比，鞘氨醇单胞菌属的两种细菌在腺癌中显著减少（P < 0.01）。有趣的是，黏附试验结果表明，用WGA-磁性颗粒偶联物提取的具有多价唾液酸和（N-乙酰葡糖胺）n结构的糖蛋白（25 - 100μg/ml）显著降低（P < 0.0001）黏液鞘氨醇单胞菌对肺癌细胞（A-549）的黏附及毒性。这些发现表明，蛋白质糖基模式可以抑制促癌的肿瘤微生物以阻断癌症进展，为推动疾病进展的分子机制提供了见解，并有助于开发新的治疗策略。
